tbuckley/cabot-search huggingface dataset:
AML classification in the year 2023: How to avoid a Babylonian confusion of languages
Authors: Sandra Huber, Constance Baer, Stephan Hutter, Frank Dicker, Manja Meggendorfer, Christian Pohlkamp, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach, Gregor Hoermann
Journal: Leukemia (2023)

In parallel to the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO 2022), an alternative International Consensus Classification (ICC) has been proposed. To evaluate the impact of the new classifications on AML diagnoses and ELN-based risk classification, we analyzed 717 MDS and 734 AML non-therapy-related patients diagnosed according to the revised 4th WHO edition (WHO 2017) by whole genome and transcriptome sequencing. In both new classifications, the purely morphologically defined AML entities decreased from 13% to 5%. Myelodysplasia-related (MR) AML increased from 22% to 28% (WHO 2022) and 26% (ICC). Other genetically-defined AML remained the largest group, and the abandoned AML-RUNX1 was mainly reclassified as AML-MR (WHO 2022: 77%; ICC: 96%). Different inclusion criteria of AML-CEBPA and AML-MR (i.a. exclusion of TP53 mutated cases according to ICC) were associated with differences in overall survival. In conclusion, both classifications focus on more genetics-based definitions with similar basic concepts and a large degree of agreement. The remaining non-comparability (e.g., TP53 mutated AML) needs additional studies to definitely answer open questions on disease categorization in an unbiased way.
Spatial single cell analysis of tumor microenvironment remodeling pattern in primary central nervous system lymphoma
Authors: Yuan Xia, Tao Sun, Guosheng Li, Mingying Li, Dongmei Wang, Xiuhua Su, Jingjing Ye, Chunyan Ji
Journal: Leukemia (2023)

Abstract To determine the overall tumor microenvironment (TME), characteristics, and transition mechanisms in primary central nervous system lymphoma (PCNSL), we performed spatial transcriptomics and matched the corresponding single-cell sequencing data of PCNSL patients. We found that tumor cells may achieve a “TME remodeling pattern” through an “immune pressure-sensing model”, in which they could choose to reshape the TME into a barrier environment or a cold environment according to the immune pressure. A key FKBP5 + tumor subgroup was found to be responsible for pushing tumors into the barrier environment, which provides a possible way to evaluate the stage of PCNSL. The specific mechanism of the TME remodeling pattern and the key molecules of the immune pressure-sensing model were identified through the spatial communication analysis. Finally, we discovered the spatial and temporal distributions and variation characteristics of immune checkpoint molecules and CAR-T target molecules in immunotherapy. These data clarified the TME remodeling pattern of PCNSL, provided a reference for its immunotherapy, and provided suggestions for the TME remodeling mechanism of other cancers.
Circulating biosignatures in multiple myeloma and their role in multidrug resistance
Authors: S. Rajeev Krishnan, M. Bebawy
Journal: Molecular Cancer (2023)

Abstract A major obstacle to chemotherapeutic success in cancer treatment is the development of drug resistance. This occurs when a tumour fails to reduce in size after treatment or when there is clinical relapse after an initial positive response to treatment. A unique and serious type of resistance is multidrug resistance (MDR). MDR causes the simultaneous cross resistance to unrelated drugs used in chemotherapy. MDR can be acquired through genetic alterations following drug exposure, or as discovered by us, through alternative pathways mediated by the transfer of functional MDR proteins and nucleic acids by extracellular vesicles (M Bebawy V Combes E Lee R Jaiswal J Gong A Bonhoure GE Grau, 23 9 1643 1649, 2009). Multiple myeloma is an incurable cancer of bone marrow plasma cells. Treatment involves high dose combination chemotherapy and patient response is unpredictable and variable due to the presence of multisite clonal tumour infiltrates. This clonal heterogeneity can contribute to the development of MDR. There is currently no approved clinical test for the minimally invasive testing of MDR in myeloma. Extracellular vesicles comprise a group of heterogeneous cell-derived membranous structures which include; exosomes, microparticles (microvesicles), migrasomes and apoptotic bodies. Extracellular vesicles serve an important role in cellular communication through the intercellular transfer of cellular protein, nucleic acid and lipid cargo. Of these, microparticles (MPs) originate from the cell plasma membrane and vary in size from 0.1-1um. We have previously shown that MPs confer MDR through the transfer of resistance proteins and nucleic acids. A test for the early detection of MDR would benefit clinical decision making, improve survival and support rational drug use. This review focuses on microparticles as novel clinical biomarkers for the detection of MDR in Myeloma and discusses their role in the therapeutic management of the disease.
The impact of artificial intelligence on the reading times of radiologists for chest radiographs
Authors: Hyun Joo Shin, Kyunghwa Han, Leeha Ryu, Eun-Kyung Kim
Journal: npj Digital Medicine (2023)

Abstract Whether the utilization of artificial intelligence (AI) during the interpretation of chest radiographs (CXRs) would affect the radiologists’ workload is of particular interest. Therefore, this prospective observational study aimed to observe how AI affected the reading times of radiologists in the daily interpretation of CXRs. Radiologists who agreed to have the reading times of their CXR interpretations collected from September to December 2021 were recruited. Reading time was defined as the duration in seconds from opening CXRs to transcribing the image by the same radiologist. As commercial AI software was integrated for all CXRs, the radiologists could refer to AI results for 2 months (AI-aided period). During the other 2 months, the radiologists were automatically blinded to the AI results (AI-unaided period). A total of 11 radiologists participated, and 18,680 CXRs were included. Total reading times were significantly shortened with AI use, compared to no use (13.3 s vs. 14.8 s, p &lt; 0.001). When there was no abnormality detected by AI, reading times were shorter with AI use (mean 10.8 s vs. 13.1 s, p &lt; 0.001). However, if any abnormality was detected by AI, reading times did not differ according to AI use (mean 18.6 s vs. 18.4 s, p = 0.452). Reading times increased as abnormality scores increased, and a more significant increase was observed with AI use (coefficient 0.09 vs. 0.06, p &lt; 0.001). Therefore, the reading times of CXRs among radiologists were influenced by the availability of AI. Overall reading times shortened when radiologists referred to AI; however, abnormalities detected by AI could lengthen reading times.
Anti‐PD1 therapy outcome can be predicted by pre‐therapy IFN‐I responsiveness of T<sub>eff</sub> cells
Authors: Melanie Grandits, Jitesh Chauhan, Heather J. Bax
Journal: Allergy (2023)

M.G., J.C. and H.J.B have been employed through a fund provided by Epsilogen Ltd. H.J.B. declares patents on antibodies for cancer.
The One Health approach for allergic diseases and asthma
Authors: Marek Jutel, Giselle S. Mosnaim, Jonathan A. Bernstein, Stefano del Giacco, David A. Khan, Kari C. Nadeau, Isabella Pali‐Schöll, Maria J. Torres, Magdalena Zemelka‐Wiacek, Ioana Agache
Journal: Allergy (2023)

Abstract The One Health approach is a collaborative and interdisciplinary strategy with focal point on human, animal, and environmental health interconnections. One Health can support the advanced management of allergic diseases and asthma, as complex, multifactorial diseases driven by interactions between the resilience response to the exposome. According to the One Health concept allergic diseases and asthma arising from exposures to a wide range of allergens, infectious agents and irritants (such as pollutants) occurring indoors and outdoors can be heavily influenced by environmental health (air, water, and soil quality) intermingled with animal health. These are currently heavily impacted by climate change, land use, urbanization, migration, overpopulation, and many more. Thus, a coordinated response to address the underlying factors that contribute to the development of allergic diseases and asthma needs to focus on the environment, human, and animal health altogether. Collaborative efforts across multiple sectors, including public health, veterinary medicine, environmental science, and community engagement are thus needed. A wide range of activities, including monitoring and surveillance of environmental and health data, targeted interventions to reduce exposures to allergens and irritants, and research on the underlying mechanisms that drive the development of allergic diseases and asthma are needed to move the field forward. In this consensus document elaborated by the European Academy of Allergy and Clinical Immunology (EAACI) and American Academy of Allergy, Asthma, and Immunology (AAAAI) under the practical allergy (PRACTALL) series, we provide insights into the One Heath approach aiming to provide a framework for addressing the complex and multifactorial nature of allergic diseases and asthma.
Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial
Authors: Hua Jin, Yu Zhang, Sijian Yu, Xin Du, Na Xu, Ruoyang Shao, Dongjun Lin, Yanqiu Chen, Jie Xiao, Zhiqiang Sun, Lan Deng, Xinquan Liang, Hongyu Zhang, Ziwen Guo, Min Dai, Pengcheng Shi, Fen Huang, Zhiping Fan, Zhao Yin, Li Xuan, Ren Lin, Xuejie Jiang, Guopan Yu, Qifa Liu
Journal: Journal of Hematology & Oncology (2023)

Abstract Background Relapsed or refractory acute myeloid leukemia (R/R AML) has a dismal prognosis. The aim of this study was to investigate the activity and tolerability of venetoclax combined with azacitidine plus homoharringtonine (VAH) regimen for R/R AML. Methods This phase 2 trial was done at ten hospitals in China. Eligible patients were R/R AML (aged 18–65 years) with an Eastern Cooperative Oncology Group performance status of 0–2. Patients received venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3–14) and azacitidine (75 mg/m 2 on days 1–7) and homoharringtonine (1 mg/m 2 on days 1–7). The primary endpoint was composite complete remission rate [CRc, complete response (CR) plus complete response with incomplete blood count recovery (CRi)] after 2 cycles of treatment. The secondary endpoints include safety and survival. Results Between May 27, 2020, and June 16, 2021, we enrolled 96 patients with R/R AML, including 37 primary refractory AML and 59 relapsed AML (16 relapsed after chemotherapy and 43 after allo-HSCT). The CRc rate was 70.8% (95% CI 60.8–79.2). In the patients with CRc, measurable residual disease (MRD)-negative was attained in 58.8% of CRc patients. Accordingly, overall response rate (ORR, CRc plus partial remission (PR)) was 78.1% (95% CI 68.6–85.4). At a median follow-up of 14.7 months (95% CI 6.6–22.8) for all patients, median overall survival (OS) was 22.1 months (95% CI 12.7–Not estimated), and event-free survival (EFS) was 14.3 months (95% CI 7.0–Not estimated). The 1-year OS was 61.5% (95% CI 51.0–70.4), and EFS was 51.0% (95% CI 40.7–60.5). The most common grade 3–4 adverse events were febrile neutropenia (37.4%), sepsis (11.4%), and pneumonia (21.9%). Conclusions VAH is a promising and well-tolerated regimen in R/R AML, with high CRc and encouraging survival. Further randomized studies are needed to be explored. Trial registration clinicaltrials.gov identifier: NCT04424147.
Synthetic electronic health records generated with variational graph autoencoders
Authors: Giannis Nikolentzos, Michalis Vazirgiannis, Christos Xypolopoulos, Markus Lingman, Erik G. Brandt
Journal: npj Digital Medicine (2023)

Data-driven medical care delivery must always respect patient privacy-a requirement that is not easily met. This issue has impeded improvements to healthcare software and has delayed the long-predicted prevalence of artificial intelligence in healthcare. Until now, it has been very difficult to share data between healthcare organizations, resulting in poor statistical models due to unrepresentative patient cohorts. Synthetic data, i.e., artificial but realistic electronic health records, could overcome the drought that is troubling the healthcare sector. Deep neural network architectures, in particular, have shown an incredible ability to learn from complex data sets and generate large amounts of unseen data points with the same statistical properties as the training data. Here, we present a generative neural network model that can create synthetic health records with realistic timelines. These clinical trajectories are generated on a per-patient basis and are represented as linear-sequence graphs of clinical events over time. We use a variational graph autoencoder (VGAE) to generate synthetic samples from real-world electronic health records. Our approach generates health records not seen in the training data. We show that these artificial patient trajectories are realistic and preserve patient privacy and can therefore support the safe sharing of data across organizations.
Mitigating age-related somatic mutation burden
Authors: Jan Vijg, Björn Schumacher, Abdulkadir Abakir, Michael Antonov, Chris Bradley, Alex Cagan, George Church, Vadim N. Gladyshev, Vera Gorbunova, Alexander Y. Maslov, Wolf Reik, Samim Sharifi, Yousin Suh, Kenneth Walsh
Journal: Trends in Molecular Medicine (2023)

Genomes are inherently unstable and require constant DNA repair to maintain their genetic information. However, selective pressure has optimized repair mechanisms in somatic cells only to allow transmitting genetic information to the next generation, not to maximize sequence integrity long beyond the reproductive age. Recent studies have confirmed that somatic mutations, due to errors during genome repair and replication, accumulate in tissues and organs of humans and model organisms. Here, we describe recent advances in the quantitative analysis of somatic mutations in vivo. We also review evidence for or against a possible causal role of somatic mutations in aging. Finally, we discuss options to prevent, delay or eliminate de novo, random somatic mutations as a cause of aging.
IgE receptor of mast cells signals mediator release and inflammation via adaptor protein 14-3-3ζ
Authors: Kwok Ho Yip, Jessica Chao, Carl Coolen, Harshita Pant, Anita Kral, William Smith, Quenten Schwarz, Michele A. Grimbaldeston, Stuart Pitson, Angel F. Lopez, Joanna Woodcock, Damon J. Tumes
Journal: Journal of Allergy and Clinical Immunology (2023)
Reply to Mauricio Plata, Cesar Diaz Ritter, and Nicolás Badillo’s Letter to the Editor re: Gabriela Ilie, Ricardo Rendon, Ross Mason, et al. A Comprehensive 6-mo Prostate Cancer Patient Empowerment Program Decreases Psychological Distress Among Men Undergoing Curative Prostate Cancer Treatment: A Randomized Clinical Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2023.02.009
Authors: Gabriela Ilie, Robert David Harold Rutledge
Journal: European Urology (2023)
Biological resilience and aging: Activation of stress response pathways contributes to lifespan extension
Authors: Sonja K. Soo, Zenith D. Rudich, Bokang Ko, Alibek Moldakozhayev, Abdelrahman AlOkda, Jeremy M. Van Raamsdonk
Journal: Ageing Research Reviews (2023)

While aging was traditionally viewed as a stochastic process of damage accumulation, it is now clear that aging is strongly influenced by genetics. The identification and characterization of long-lived genetic mutants in model organisms has provided insights into the genetic pathways and molecular mechanisms involved in extending longevity. Long-lived genetic mutants exhibit activation of multiple stress response pathways leading to enhanced resistance to exogenous stressors. As a result, lifespan exhibits a significant, positive correlation with resistance to stress. Disruption of stress response pathways inhibits lifespan extension in multiple long-lived mutants representing different pathways of lifespan extension and can also reduce the lifespan of wild-type animals. Combined, this suggests that activation of stress response pathways is a key mechanism by which long-lived mutants achieve their extended longevity and that many of these pathways are also required for normal lifespan. These results highlight an important role for stress response pathways in determining the lifespan of an organism.
Learning what and where to segment: A new perspective on medical image few-shot segmentation
Authors: Yong Feng, Yonghuai Wang, Honghe Li, Mingjun Qu, Jinzhu Yang
Journal: Medical Image Analysis (2023)

Traditional medical image segmentation methods based on deep learning require experts to provide extensive manual delineations for model training. Few-shot learning aims to reduce the dependence on the scale of training data but usually shows poor generalizability to the new target. The trained model tends to favor the training classes rather than being absolutely class-agnostic. In this work, we propose a novel two-branch segmentation network based on unique medical prior knowledge to alleviate the above problem. Specifically, we explicitly introduce a spatial branch to provide the spatial information of the target. In addition, we build a segmentation branch based on the classical encoder-decoder structure in supervised learning and integrate prototype similarity and spatial information as prior knowledge. To achieve effective information integration, we propose an attention-based fusion module (AF) that enables the content interaction of decoder features and prior knowledge. Experiments on an echocardiography dataset and an abdominal MRI dataset show that the proposed model achieves substantial improvements over state-of-the-art methods. Moreover, some results are comparable to those of the fully supervised model. The source code is available at github.com/warmestwind/RAPNet.
Digging the intercellular crosstalk via extracellular vesicles: May exosomes be the drug delivery solution for target glioblastoma?
Authors: Ana Macedo-Pereira, Cláudia Martins, Jorge Lima, Bruno Sarmento
Journal: Journal of Controlled Release (2023)

Glioblastoma (GBM) is an adult's most aggressive brain tumor. The advances in molecular pathology and cell signaling pathways have deepened researchers' understanding of intercellular communication mechanisms that can induce tumor progression, namely the release of extracellular vesicles. Exosomes are small extracellular vesicles in various biological fluids released by almost all cells, thus carrying various biomolecules specific to their parental cell. Several pieces of evidence indicate that exosomes mediate intercellular communication in the tumor microenvironment and cross the blood-brain barrier (BBB), valuable tools for diagnostic and therapeutic applications under the scope of brain diseases such as brain tumors. This review aims to resume the several biological characteristics and the interplay between glioblastoma and exosomes, describing highlight studies that demonstrate the role of exosomes in the tumor microenvironment of GBM and their potential for non-invasive diagnoses and therapeutic approaches, namely, as nanocarriers for drug or gene delivery and cancer vaccines.
Duration of type 2 diabetes and liver-related events in nonalcoholic fatty liver disease: A landmark analysis
Authors: Xinrong Zhang, Terry Cheuk-Fung Yip, Yee-Kit Tse, Vicki Wing-Ki Hui, Guanlin Li, Huapeng Lin, Lilian Yan Liang, Jimmy Che-To Lai, Henry Lik-Yuen Chan, Stephen Lam Chan, Alice Pik-Shan Kong, Grace Lai-Hung Wong, Vincent Wai-Sun Wong
Journal: Hepatology (2023)

Background and Aims: We aimed to determine the impact of the duration of type 2 diabetes (T2D) on the risk of liver-related events and all-cause mortality in patients with NAFLD. Approach and Results: We conducted a territory-wide cohort study of adult patients with NAFLD diagnosed between January 1, 2000, and July 31, 2021, in Hong Kong. T2D was defined by the use of any antidiabetic agents, laboratory tests, and/or diagnosis codes. The primary endpoint was liver-related events, defined as a composite endpoint of HCC and cirrhotic complications. To conduct a more granular assessment of the duration of T2D, we employed landmark analysis in four different ages of interest (biological age of 40, 50, 60, and 70 years). By multivariable analysis with adjustment of non–liver-related deaths, compared with patients without diabetes at age 60 (incidence rate of liver-related events: 0.70 per 1,000 person-years), the adjusted subdistribution HR (SHR) of liver-related events was 2.51 (95% CI: 1.32–4.77; incidence rate: 2.26 per 1,000 person-years) in patients with T2D duration &lt; 5 years, 3.16 (95% CI: 1.59–6.31; incidence rate: 2.54 per 1,000 person-years) in those with T2D duration of 6–10 years, and 6.20 (95% CI: 2.62–14.65; incidence rate: 4.17 per 1000 person-years) in those with T2D duration more than 10 years. A similar association between the duration of T2D and all-cause mortality was also observed. Conclusions: Longer duration of T2D is significantly associated with a higher risk of liver-related events and all-cause mortality in patients with NAFLD.